The overall objective of the project is to develop a nicotine transdermal delivery system (TDS) as an aid to smoking cessation. The TDS will maintain stable blood levels of nicotine, approximately 10 ng/ml, for 24 hours. The feasibility of the project was demonstrated in a Phase I SBIR study. High transdermal nicotine fluxes, 26.1 mg/cm2/day, were demonstrated in vitro, and the effects of vehicle composition, pH, and nicotine concentration investigated. In vivo transdermal delivery was demonstrated in a new hairless guinea pig model. Flux was directly dependent on nicotine concentration. The TDS did not cause skin irritation in rabbits. During Phase II development of the nicotine TDS will continue based on the Phase I results. Prototypes will be evaluated for transdermal flux in vitro and for transdermal flux and achieved blood levels in vivo in hairless guinea pigs. Preclinical studies and manufacturing processes and specifications will be documented and an IND application filed. To conclude SBIR Phase II, initial human clinical studies for safety and nicotine blood levels will be conducted. The results of the Phase II studies will be the basis for obtaining support from the pharmaceutical industry for continued clinical studies and commercialization.